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多巴胺D1受体在Sf9昆虫细胞中的表达及左旋氯代斯阔任对重组D1受体的激动作用(英文)

Expression of dopamine D1 receptor in Sf9 insect cells and agonism of 1-12-chloroscoulerine on recombinant D1 receptor

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【作者】 和友; 金文桥; 申庆祥; 陈新建; 金国章;

【Author】 HE You, JIN Wen-Qiao~2, SHEN Qing-Xiang~3, CHEN Xin-Jian, JIN Guo-Zhang Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031;3~Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China

【机构】 中国科学院上海生命科学研究院药物研究所; 上海市计划生育研究所; 上海市计划生育研究所 上海 200031; 上海 200031; 上海 200032 中国; 上海 200032 中国;

【摘要】 目的:在Sf9昆虫细胞中表达D1受体,并研究左旋氯代斯阔任对重组D1受体的激动作用。方法:构建含D1受体cDNA的重组杆状病毒,以其感染Sf9昆虫细胞得到D1受体表达。[3H]SCH23390受体结合检测重组D1受体的药理特性。[3H]SCH23390受体结合和cAMP测定实验检测左旋氯代斯阔任对重组D1受体的激动作用。结果:在Sf9昆虫细胞中成功表达D1受体,[3H]SCH23390与重组D1受体最大结合量(Bmax)为(0.94±0.06)nmol/g蛋白,[3H]SCH23390与重组D1受体的结合解离常数(Kd)为(1.9±0.3)nmol/L,其药理特性与小牛纹状体脑匀浆所得结果一致。左旋氯代斯阔任对重组D1受体有高亲和力,解离常数Ki为(6.3±1.4)nmol/L;并剂量依赖地引起胞内cAMP增加,EC50为0.72μmol/L(95%可信限为0.67-0.77μmol/L),表现出D1激动作用。结论:在杆状病毒/昆虫细胞Sf9中,成功建立了D1受体异源表达系统。在细胞分子水平,直接证实了左旋氯代斯阔任对D1受体的激动作用。

【Abstract】 AIM: To express dopamine D1 receptor in baculovirus-Sf9 cell system, and to investigate the effects of l-12-chloroscoulerine (l-CSL) on the recombinant D1 receptor (D1R). METHODS: The recombinant baculovirus, Autographa californica nuclear polyhedrosis virus bearing D1R (AcNPV- D1R) was generated, and then was used to produce recombinant D1R in Sf9 insect cells. Expression of D1R in Sf9 cells was monitored by [3H]SCH23390 binding assay. The effects of l-CSL on recombinant D1R were investigated by [3H]SCH23390 binding assay and cAMP assay. RESULTS: The recombinant baculovirus AcNPV bearing D1R cDNA was generated, and was successfully expressed in Sf9 insect cells. The expression level of (Bmax) was (0.94±0.06) nmol/g protein. The Kd value of [3H]SCH23390 was (1.9±0.3) nmol/L, which was consistent with the previous results from calf striutam tissues. l-CSL had a high affinity to recombinant D1R with Ki value of (6.3±1.4) nmol/L, and increased the intracellular cAMP level in a concentration-dependent manner with EC50 value of 0.72 μmol/L and 95% confidence limit was 0.67-0.77 μmol/L. Thus l-CSL has the D1 receptor agonism. CONCLUSION: An efficient baculovirus Sf9 insect cell system for dopamine D1 receptor was constructed and l-CSL presented the D1 receptor agonism on cellular-molecular level directly.

【基金】 Project supported by the National Natural Science Foundation of China (№ 30070866) and Grant G (1998) 051126 from the Ministry of Science and Technology of China.
  • 【文献出处】 Acta Pharmacologica Sinica ,中国药理学报(英文版) , 编辑部邮箱 ,2003年03期
  • 【分类号】R96
  • 【下载频次】58
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